(176f) Integrating Design for Six Sigma Tools and Qbd Concepts In Hot Melt Extrusion Process Development

This work summarizes how the Design for Six Sigma (DFSS) tool set was employed as a means to streamline delivery of Quality by Design (QbD) for a hot melt extrusion process. DFSS methodology was believed to provide an efficient means to capture the key components of both the systematic approach to development and risk management elements that are central to QbD. While various roadmaps exist for DFSS, the one that was utilized was CDOV or Concept-Design-Optimize-Verify.

DFSS Concept stage tools helped manage and translate existing knowledge - including experimental information, first principles understanding, models and best practices gleaned from peer reviewed literature - into a rationalized, systematic approach to development. This was achieved through process mapping activities combined with a quality function deployment grid that helped clarify and prioritize development targets. As such, a daunting, technically complex process became a more manageable set of potential critical process parameters to evaluate first. These parameters were thought to have the most impact in achieving the desired quality requirement of a molecularly dispersed, extruded product.

Successive DFSS Design stage tools utilized statistically designed experiments facilitated by first principles understanding and modeling. Initial screening experiments sought to help define the Critical Quality Attributes (CQA) and intentionally included perceived failure points. Even though these failure points were known to be sufficiently removed from the anticipated commercial operating space, the thought was a better understanding of failure would yield better definition of CQA's. The initial experiments successfully identified several key CQA's, and a single critical process parameter (CPP) having the most impact on product quality.

At this point, DFSS Optimization stage tools assisted in expanding process understanding and enhancing robustness, moving towards a defined design space. Response surface mapping experiments were completed to identify the curvature and interactions of the CPP in the vicinity of the anticipated commercial operating range. Throughout these experiments, PAT was heavily integrated. While a control strategy was not included in the scope of this work, the robustness testing that PAT facilitated provided a strong starting point for later formulating a control strategy.

Ultimately, the DFSS tools helped manage the technical complexity of developing this hot melt extrusion process and deliver on QbD. Decisions and assumptions throughout the development process were clearly spelled out, with CQA's and CPP's identified. The knowledge gained from this development exercise facilitated process optimization, and yielded a robust, well defined design space.